Hypercalcemia Definition: 1. Hypercalcemiaypercalcemia is defined as a serum calcium > 10.5 mg/dlmg/dl and severe hypercalemia is defined as a serum calcium > 14 mg/dlmg/dl (> 3.5 mmol/L)mmol/L).... 2. A hypercalcemic crisis is present when severe neurological symptoms or cardiac arrhythmias are present in a patient with a serum calcium > 14 mg/dl (> 3.5 mmol/L) or when the serum calcium is > 16 mg/dl (> 4 mmol/L) I Causes A. Malignancy 1. Breast Cancer with bone metastases 2. Lung Cancer 3. Head and Neck squamous cell cancer 4. Renal Cell Cancer 5. Hematologic a. Multiple Myeloma b. Hodgkin's Lymphoma B. Paget's Disease of Bone C. Hyperparathyroidism 1. Primary Hyperparathyroidism (most common cause) a. May be associated with multiple endocrine neoplasia 2. Tertiary Hyperparathyroidism D. Medications 1. Thiazide Diuretic s 2. Lithium 3. Vitamin A toxicity 4. Vitamin D toxicity (e.g. 25-Hydroxyvitamin D2) 5. Milk alkali syndrome E. Endocrine 1. Adrenal Insufficiency 2. Thyrotoxicosis ( Hyperthyroidism ) 3. Pheochromocytoma 4. Acromegaly F. Other causes 1. Familial hypocalciuric hypercalcemia 2. Prolonged immobilization 3. Granulomatous disease ( Sarcoidosis , Tuberculosis ) II. Symptoms and Signs A. Often asymptomatic B. Symptoms and Signs are related to Serum Calcium Levels 1. Calcium > 11.5 mg/dl (2.9 mmol/L) a. Symptom onset 2. Calcium > 13 mg/dl (3.2 mmol/L) a. Nephrocalcinosis b. Acute Renal Failure C. General Symptoms 1. See complication-specific symptoms below 2. Nausea 3. Headache 4. Diarrhea 5. Anorexia 6. Lethargy 7. Pruritus (Metastatic calcification of skin) III. Imaging A. Calcified soft tissues IV. Labs and Diagnostics A. Serum Calcium increased 1. Total Serum Calcium > 10.5 mg/dl 2. Ionized Calcium >5.6 mg/dl B. Electrocardiogram 1. Shortened QT Interval 2. Tall U Wave 3. Bradycardia V. Evaluation A. General 1. Primary hyperparathroidism and cancer: 90% of cases B. Step 1: Confirm hypercalcemia present (see labs above) C. Step 2: Obtain history for potential causes 1. See causes above 2. Eliminate potential causative medications D. Step 3: Obtain intact Parathyroid Hormone (PTH) Level 1. PTH low: Go to Step 4 2. PTH normal or high: Obtain 24 hour Urine Calcium a. 24 hour Urine Calcium normal (4mg/kg/d ) or high i. Primary Hyperparathyroidism ii. Recovery from Acute Tubular Necrosis iii. Lithium therapy b. 24 hour Urine Calcium low i. Familial hypocalciuric hypercalcemia Calcium to Creatinine ratio <0.01 E. Step 4: Assess for malignancy and endocrinopathy 1. Careful history and examination for tumor 2. Endocrine Labs a. Thyroid Stimulating Hormone ,free T4, ( Hyperthyroidism ) 3. Reconsider medication causes of low PTH a. Thiazide Diuretic s b. Excessive Vitamin D Intake c. Excessive Vitamin A Intake d. Milk-Alkali Syndrome VI. Management General principle: Patients with calcium levels greater than 14 mg per dL (3.5 mmol per L) or symptomatic patients with calcium levels greater than 12 mg per dL (3 mmol per L) should be immediately and aggressively treated. A. Identify and treat underlying cause B. Mild Hypercalcemia ( Serum Calcium <12 mg/dl) 1. Adequate Hydration (>2 Liters per day) 2. Maximize mobility 3. Diuretics if symptomatic a. Furosemide ( Lasix ) 40-160 mg/day C. Severe hypercalcemia ( Serum Calcium >14 mg/dl) 1. Consider also in moderate symptomatic hypercalcemia 2. Normal Saline 2 to 4 Liters/day for 1-3 days a. Adjust to obtain 200 ml urine output per hour b. Exercise caution in Congestive Heart Failure c. Anticipate 1-3 mg/dl drop in Serum Calcium 3. Additional measures if refractory after hydration a. Lasix 10-20 mg q1-2 hours as needed b. Calcitonin 4-8 IU/kg IM or SQ q6 hours for 24 hours 4. Agents with specific indications a. Malignancy: Bisphosphonates i. Pamidronate ( Aredia ) 60-90 mg IV over 4 hours b. Vitamin D toxicity, Lymphoma , Myeloma or Granuloma i. Hydrocortisone 200 mg IV qd for 3 days .